Predicting Electrophiles for Multi-Component Reactions

  • By Jenny Stein
  • 14 October 2020

Dr. Peng Liu and collaborators published an article in Chem, “Compatibility Score for Rational Electrophile Selection in Pd/NBE Cooperative Catalysis”. 

Developing catalytic methods for novel types of chemical bond formation using readily available starting materials has been a long-term goal in organic synthesis.

While traditional cross-coupling reactions take place between a nucleophile and an electrophile, various coupling reactions involving two different electrophiles have recently emerged. These reactions provide promising platforms for synthesizing functionalized molecules, considering the large variety of commercially available carbon and heteroatom electrophiles.

However, it is not trivial to identify what electrophile starting materials may be used together, because they must have orthogonal reactivity that allows them to react selectively with different organometallic species in different elementary steps of the catalytic cycle. This work describes a computational quantum mechanical modeling method to calculate the electrophile compatibility score (ECS), which can be used to predict whether two electrophile starting materials are compatible with each other. Therefore, this approach can rapidly identify effective electrophiles in multi-electrophile coupling reactions.